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David Granville



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Name / Full Titles / Contact Information:

David J. Granville, Ph.D.

Assistant Professor/Canada Research Chair

U.B.C. McDonald Research Laboratory / The iCAPTURE Centre

Room 375, Burrard West

St. Paul’s Hospital, Burrard Building,

1081 Burrard Street, Vancouver, B.C. V6Z 1Y6

Canada

Phone: (604) 806-9267

Fax: (604) 806-9274

Email: dgranville@mrl.ubc.ca

URL: http://www.chairs.gc.ca/english/profile/viewprofile.cfm?ID=210



Bio/ Short Paragraph:

Dr. David Granville is an Assistant Professor/Canada Research Chair in the Department

of Pathology and Laboratory Medicine at the University of British Columbia (UBC). Dr.

Granville completed his B.Sc. in Molecular Biology at Simon Fraser University (SFU). He was

involved in the co-operative education program at SFU; obtaining valuable training at the

Animal Diseases Research Institute (Lethbridge, AB), the Bureau of Microbial Hazards (Ottawa,

ON), Biomedical Research Centre (Vancouver, BC) and Quadra Logic Technologies

(Vancouver, BC). Upon graduation in 1994, he joined QLT Inc., where he worked as a

technician (1994-1996), Research Associate (1996-2000) and finally as a Scientist (2000-2001),

respectively, in the Immunology and Cell Biology division of Preclinical Pharmacology. Dr.

Granville’s work at QLT was primarily devoted to elucidating the cellular and biochemical mode

of action of porphyrin-derived photosensitizers. In particular, much of his work was focused on

verteporfin (Visudyne®) which is now clinically approved for the treatment of age related

macular degeneration (ARMD), the leading cause of blindness in the elderly. His research has

revealed several key mechanisms by which photodynamic therapy may act upon the

neovasculature in the treatment of cancer and ARMD as well as its effects on smooth muscle

cells (SMC) which is relevant for the treatment of atherosclerosis, restenosis and transplant

vascular disease.

Dr. Granville completed his Ph.D. studies at UBC under the supervision of Dr. Bruce

McManus and was funded by a Heart and Stroke Foundation of Canada Research Traineeship.

Over the past five years, David has published over 38 original research or review articles,

including 3 book chapters and 4 patents (2 pending) related to the mechanisms and regulation of

apoptosis in a number of cell types and cardiovascular diseases such as atherosclerosis, viral

myocarditis, myocardial infarction (heart attack) and heart transplant rejection. In 2001, Dr.

Granville decided to leave QLT and was offered a position in the laboratory of Dr. Roberta

Gottlieb at the prestigious Scripps Research Institute (La Jolla, CA). Dr. Granville was awarded

a CIHR post-doctoral fellowship to study the role and regulation of cell death in cardiac ischemia

and reperfusion injury. In particular, his research was focused on mitochondrial and endoplasmic

reticular regulation of cell death. Dr. Granville demonstrated that inhibition of a specific subset

of cytochrome p450 monooxygenases (CYP) reduces the extent of myocardial cell death and

improves heart recovery following ischemia and reperfusion.

Dr. Granville was recruited back to UBC in May, 2003 as a Tier II Canada Research

Chair (www.chairs.gc.ca) and was awarded a start-up grant from the Canada Foundation for

Innovation ($350,000). His research at iCAPTUR4E is currently focused on delineating the

causation and biochemical mechanisms of endothelial and smooth muscle cell death in the

context of native atherosclerosis and transplant vascular disease. In specific, his research is

devoted towards understanding the role of mitochondrial and endoplasmic reticular apoptosis

pathways in endothelial and smooth muscle cells in response to Granzyme B, FasL, TRAIL,

oxLDL and other factors known to be present in atheromatous plaque.



Education / Training:



Simon Fraser University, Burnaby, BC; Molecular Biology, 1989-1994

University of British Columbia, Vancouver, BC, Pathology and Laboratory Medicine, 1997-

2000

QLT Inc., Vancouver, BC; Preclinical Pharmacology (Immunology and Cell Biology), 1994-

2001

The Scripps Research Institute, La Jolla, CA; Department of Molecular and Experimental

Medicine, 2001-2003.





Recent Publications:

(****all references are linked to PubMed)



Granville, D.J., Carthy, C.M., Hunt, D.W.C. and McManus, B.M. (1998) Apoptosis: molecular

aspects of cell death and disease. Lab. Invest. 78:893-913.



Koglin, J., Granville, D.J., Glysing-Jensen, T., Mudgett, J.S., Carthy, C.M., McManus, B.M.

and Russel, M.E. (1998) Attenuated acute cardiac rejection in NOS2-/- recipients correlates with

reduced apoptosis. Circulation. 99:836-842.



Granville, D.J., An, M.T., Levy, J.G., McManus, B.M. and Hunt, D.W.C. (1999) Bcl-2

overexpression blocks caspase activation and downstream apoptotic events instigated by

photodynamic therapy. Br. J. Cancer 79:95-100.



Granville, D.J., Shaw, J.R., Leong, S., Carthy, C.M., Margaron, P., Hunt, D.W. and McManus,

B.M. (1999) Release of cytochrome c, Bax migration, Bid cleavage and activation of multiple

caspases during endothelial cell apoptosis. Am. J. Pathol. 155:1021-1025.



Dong, C., Granville, D.J., Tuffnel, C.E., Kenyon, J., English, D., Wilson, J.E. and McManus,

B.M. (1999) Bax and apoptosis in acute and chronic rejection of rat cardiac allografts. Lab.

Invest. 79:1643-1653.

Granville, D.J., Carthy, C.M., Jiang, H., Levy, J.G., McManus, B.M., Matroule, J.Y., Piette, J. and

Hunt, D.W.C. (2000) NF-B activation by the photochemotherapeutic agent verteporfin. Blood

95:256-262.



Belzacq, A., Jacotot, E., Vieira, H.L., Mistro, D., Granville, D.J., Xie, Z., Reed, J.C., Kroemer,

G. and Brenner, C. (2001) Apoptosis induction by the photosensitizer verteporfin. Identification

of mitochondrial adenine nucleotide translocator as a critical target. Cancer Res. 61:1260-1264.



Miller, L., Granville, D.J., Narula, J. and McManus, B.M. (2001) Apoptosis in cardiac

transplant rejection. Cardiol. Clin.19(1):141-154.



Matroule, JY, Carthy, C.M., Granville, D.J., Hunt, D.W., and Piette, J. (2001) Mechanism of

colon cancer cell apoptosis by pyropheneophorbide-a methylester photosensitization. Oncogene.

20: 4070-4084.



Granville, D.J., Cassidy, B.A., Ruehlmann, D., Choy, J., Brenner, C., Kroemer, G., Margaron, P., van

Breemen, C., Hunt, D.W. and McManus, B.M. (2001) Mitochondrial release of Apoptosis Inducing

Factor (AIF) and cytochrome c during smooth muscle cell apoptosis. Am. J. Pathol. 159:305-311.



Choy, J.*, Granville, D.J.*, Hunt, D.W. and McManus, B.M. (2001) Endothelial cell apoptosis:

Biochemical characteristics and potential implications for atherosclerosis. J. Mol. Cell Cardiol. 9: 1673-

1690.



Granville, D.J., Ruehlmann, D., Choy, J., Cassidy, B.A., Hunt, D.W., van Breemen, C. and McManus,

B.M. (2001) Bcl-2 increases emptying of endoplasmic reticulum Ca2+ stores during photodynamic

therapy-induced apoptosis. Cell Calcium 30(5): 343-350.



Granville, D.J. and Gottlieb, R.A. (2002) Analyzing mitochondrial changes during apoptosis. Methods. 4:

341-347.



Choy, J.C., McDonald, P.C., Suarez, A.C., Hung, V.H., Wilson, J.E., McManus, B.M. and Granville,

D.J. (2003) Granzyme B in atherosclerosis and transplant vascular disease: Association with cell death

and atherosclerotic disease severity. Modern Pathol. (In press).



Choy, J.C., Yanagawa, B., Podor, T.J., Granville, D.J., Rezai, N., Walker, D. and McManus, B.M.

(2003) The Regulation and Consequences of Immune-Mediated Cell Death in Atheromatous Diseases.

Cardiovasc. Toxicol.(In press).



Granville, D.J. and Gottlieb, R.A. (2003) The mitochondrial voltage-dependent anion channel (VDAC)

as a therapeutic target for initiating cell death. Curr. Med. Chem. (In press).



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